NR AUSI
AU Weber,P.; Giese,A.; Piening,N.; Mitteregger,G.; Thomzig,A.; Beekes,M.; Kretzschmar,H.A.
TI Cell-free formation of misfolded prion protein with genuine prion infectivity
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Poster: Pathogenese/Infektion PATH-09
PT Konferenz-Poster
AB Prions are the causative infectious agents of transmissible spongiform encephalopathies and, thought to arise from misfolding and aggregation of prion protein (PrP)1. The structural conversion of cellular prion protein (PrPc) to the disease-associated misfolded isoform (PrPsc) can be modelled in vitro by protein misfolding cyclic amplification (PMCA)2. Wild-type hamsters challenged with proteinase resistant PrP (PrPres) generated in vitro by serial transmission PMCA showed accumulation of PrPsc in their brains and developed a neurological disease symptomatically indistinguishable from 263K hamster scrapie. PrPres generated by PMCA was associated with approximately ten times less infectivity than an equivalent quantity of brain-derived PrPsc casting doubt on the "protein-only" hypothesis of prion propagation and supporting theories invoking additional agent-derived factors. In contrast, animals challenged with PMCA-derived PrPres coupled to nitrocellulose (NC) particles exhibited cerebral PrPsc deposition and scrapie symptoms as fast as animals inoculated with NC particles incubated in infectious scrapie brain homogenate. These findings demonstrate for the first time, that the PrPres generated in vitro is as infectious as authentic brain derived PrPsc provided that confounding effects related to differences in the size distribution of PrP aggregates and consecutive differences in regard to biological clearance are abrogated by prion delivery on suitable carrier particles.
AD P.Weber, A.Giese, N.Piening, G.Mitteregger, H.A.Kretzschmar, Zentrum für Neuropathologie und Prionforschung der LMU, Feodor-Lynen-Str. 23, 81377 München; A.Thomzig, M.Beekes, Robert-Koch-Institut, Nordufer 20, 13353 Berlin
SP englisch
PO Deutschland
OR Tagungsband